Page 74 - Advanced Organic Chemistry Part B - Reactions & Synthesis

46 1.3. The Nitrogen Analogs of Enols and Enolates: Enamines
and Imine Anions
CHAPTER 1
Alkylation of Enolates
and Other Carbon The nitrogen analogs of ketones and aldehydes are called imines, azomethines,
Nucleophiles or Schiff bases, but imine is the preferred name and we use it here. These compounds
can be prepared by condensation of primary amines with ketones or aldehydes. 102 The
equilibrium constants are unfavorable, so the reaction is usually driven forward by
removal of water.

O N R'
R C R + H 2 NR' R C R + H 2 O

When secondary amines are heated with ketones or aldehydes in the presence of an
acidic catalyst, a related reaction occurs, and the product is a substituted vinylamine
or enamine.

O NR'2
+ HNR" 2 + H O
R' CH R R' CHR 2
2
There are other methods for preparing enamines from ketones that utilize strong
chemical dehydrating reagents. For example, mixing carbonyl compounds and
secondary amines followed by addition of titanium tetrachloride rapidly gives
enamines. This method is especially applicable to hindered amines. 103 Triethoxysilane
can also be used. 104 Another procedure involves converting the secondary amine to
its N-trimethylsilyl derivative. Owing to the higher affinity of silicon for oxygen than
nitrogen, enamine formation is favored and takes place under mild conditions. 105

(CH ) CHCH CH O + (CH ) SiN(CH ) (CH ) CHCH CHN(CH )
2
3 3
3 2
3 2
3 2
3 2
88%
The -carbon atom of an enamine is a nucleophilic site because of conjugation
with the nitrogen atom. Protonation of enamines takes place at the -carbon, giving
an iminium ion.
+ – H + +
R' N C CR 2 R' N C CR 2 R' N C CHR 2
2
2
2
R R R
102 For general reviews of imines and enamines, see P. Y. Sollenberger and R. B. Martin, in Chemistry of
the Amino Group, S. Patai, ed., Interscience, New York, 1968, Chap. 7; G. Pitacco and E. Valentin, in
Chemistry of Amino, Nitroso and Nitro Groups and Their Derivatives, Part 1, S. Patai, ed., Interscience,
New York, 1982, Chap. 15; P. W. Hickmott, Tetrahedron, 38, 3363 (1982); A. G. Cook, ed., Enamines,
Synthesis, Structure and Reactions, Marcel Dekker, New York, 1988.
103
W. A. White and H. Weingarten, J. Org. Chem., 32, 213 (1967); R. Carlson, R. Phan-Tan-Luu,
D. Mathieu, F. S. Ahounde, A. Babadjamian, and J. Metzger, Acta Chem. Scand., B32, 335 (1978);
R. Carlson, A. Nilsson, and M. Stromqvist, Acta Chem. Scand., B37, 7 (1983); R. Carlson and A. Nilsson,
Acta Chem. Scand., B38, 49 (1984); S. Schubert, P. Renaud, P.-A. Carrupt, and K. Schenk, Helv. Chim.
Acta, 76, 2473 (1993).
104 B. E. Love and J. Ren, J. Org. Chem., 58, 5556 (1993).
105
R. Comi, R. W. Franck, M. Reitano, and S. M. Weinreb, Tetrahedron Lett., 3107 (1973).